A cylindrical vial having a closed bottom is used to contain medicines, various test reagents, or the like. The vial has an opening which opens at the top and through which the content is put in and taken out. Around the opening a rim is formed. The opening is conventionally sealed with a closure device that comprises, for example, an aluminum protector and a seal member. The protector has a wear part on the upper surface, and to the wear part a synthetic resin cap is affixed. The seal member fits into the inner surface of the protector and seals the opening.
A medicament contained in the vial is lyophilized as follows. The seal member is attached to the vial in a state in which a flange of the seal member is not in contact with the opening (hereafter referred to as an “incompletely sealing state”), and the vial is placed in a lyophilization apparatus. In the incompletely sealing state, the seal member does not seal the opening, and the inside of the vial containing the medicament communicates with the outside via the opening. By lyophilization in this state, liquid components in the medicament are frozen and then sublimated to be removed from the vial. After the completion of the lyophilization, the seal member is pushed down so as to seal the opening (hereinafter this state is referred to as a “sealing state”). Next, the sealed vial is taken out from the lyophilization apparatus, and the skirt of the protector is wound on the seal member with the use of a winding apparatus.
The vial having the aluminum protector is made of, as constituents, four kinds of materials, which are glass, aluminum, synthetic resin, and rubber. These materials are difficult to separate during disposal. In addition, although the vial taken out from a lyophilization apparatus is sealed with the seal member, whose leg has been inserted into the opening, the sealing performance is imperfect. In order to prevent the vial from being biologically contaminated with, for example, bacteria from the outside and to ensure liquid tightness and airtightness, it is necessary to completely seal the opening by winding a protector on the seal member with the use of a winding apparatus as soon as possible after the vial is taken out from the lyophilization apparatus.
As a conventional art for solving the above problems, there has been proposed a closure device for a container, comprising a synthetic resin cap provided with a cylinder part and with a top wall, and a seal member that is to be attached to the cap (see, for example, JP-07-165252-A).
In this conventional art, the top wall has a window for needle entry, and the cylinder part hangs down from the outer circumference of the top wall. On the inner surface of the cylinder part, a locking means is disposed. The seal member fits into the inside of the cap. The seal member comprises a disk-shaped flange and a cylindrical leg hanging down from the under surface of the flange.
The vial is placed in a lyophilization apparatus with its opening provided with the closure device in the incompletely sealing state. After the completion of the lyophilization, the vial is pressed down so that the closure device is pushed down to the sealing state. In this sealing state, the flange is firmly pressed against the periphery of the vial opening by the top wall of the cap. The locking means locks at the under surface of the rim of the vial, thereby holding the cap in a state in which the seal member is firmly pressed against the upper surface of the rim by the top wall.
Transition from the incompletely sealing state to the sealing state is achieved as follows: for example, in the lyophilization apparatus, the gaps between the shelves are narrowed, and the upper shelf presses down the vial so as to push down the closure device. When the pressing force is excessively high, the vial may be damaged. Accordingly, the pressing force is set at, for example, 60 N or less. However, size variations occur in, for example, the overall height of the vial, the thickness of the flange, the horizontal level of the shelves of the lyophilization apparatus, the gaps between the multiple shelves, or the like. The size tolerance of, for example, the thickness of the flange is set at ±0.3 mm.
Especially when the vial is made of glass, the size tolerance of the overall height of the vial is set at as large as ±0.5 mm. Consequently, it is difficult to securely cap a large number of (for example, 6000) vials at a time without failures by pushing down their closure devices to the sealing state by means of the shelves that move a certain distance. The top wall of the cap may fail to firmly press down the seal member, which may result in sealing failures or decrease in airtightness.
As a conventional seal member, there exists a seal member whose upper surface has a projection that is provided between the central part for injection needle insertion and the circumference of the flange. An object of providing this projection is to offer the following advantages, which are attributed to decrease in contact area between the seal member and other things:    (1) advantage of preventing the seal members from adhering to each other in a production step of the seal member, a filling step of a medicine, or the like;    (2) advantage of preventing the seal member from adhering to the wall of a facility device in a washing step, a sterilization step, a drying step, or the like;    (3) advantage of improving the operability of a parts feeder for the seal member;    (4) advantage of preventing the top of the seal member from adhering by suction to the under surface of the shelf that pushes down the seal member to the sealing state in a lyophilization apparatus, and consequently preventing the vial from being lifted and then tipped over or damaged; and the like.
However, even when the seal member having the projection is used to securely cap the vial, the flange may not be sufficiently pushed down by the cap, which may result in sealing failure. In addition, if the size of the projection and/or the thickness of the flange is larger, the pressing force required for capping is excessively high and thus it is difficult to securely cap all the vials with the seal members.
The content of the vial is taken out according to the following process. First, from the window for needle entry located in the center of the top wall, an injection needle is inserted into the vial through the center part of the upper surface of the seal member. Next, a dissolving solution or the like is injected into the vial through the needle, and the dissolved content is pumped out with the needle. Unless the flange is firmly pressed against the upper surface of the rim by the cap, the insertion force causes the center part of the seal member to be deformed toward the inside of the vial and, as a result, the insertion may fail. This tendency is greater especially when a larger injection needle, for example, a double-ended needle, a plastic infusion needle (diameter: about 4 mm), or the like is used. Moreover, when an injection needle is obliquely inserted into the vial through the seal member, whose leg hangs down into the opening of the vial, the tip of the injection needle may accidentally stick into the leg. Upon this oblique insertion, unless the flange is firmly pressed down by the cap as described above, further insertion of the needle may draw the flange into the vial along with the leg.